tbuckley/cabot-search huggingface dataset:
Effectiveness of Monovalent and Bivalent mRNA Vaccines in Preventing COVID-19–Associated Emergency Department and Urgent Care Encounters Among Children Aged 6 Months–5 Years — VISION Network, United States, July 2022–June 2023
Authors: Ruth Link-Gelles, Allison Avrich Ciesla, Elizabeth A.K. Rowley, Nicola P. Klein, Allison L. Naleway, Amanda B. Payne, Anupam Kharbanda, Karthik Natarajan, Malini B. DeSilva, Kristin Dascomb, Stephanie A. Irving, Ousseny Zerbo, Sarah E. Reese, Ryan E. Wiegand, Morgan Najdowski, Toan C. Ong, Suchitra Rao, Melissa S. Stockwell, Ashley Stephens, Kristin Goddard, Yessica C. Martinez, Zachary A. Weber, Bruce Fireman, John Hansen, Julius Timbol, Shaun J. Grannis, Michelle A. Barron, Peter J. Embi, Sarah W. Ball, Manjusha Gaglani, Nancy Grisel, Julie Arndorfer, Mark W. Tenforde, Katherine E. Fleming-Dutra
Journal: MMWR Morbidity and Mortality Weekly Report (2023)

On June 19, 2022, the original monovalent mRNA COVID-19 vaccines were approved as a primary series for children aged 6 months-4 years (Pfizer-BioNTech) and 6 months-5 years (Moderna) based on safety, immunobridging, and limited efficacy data from clinical trials. On December 9, 2022, CDC expanded recommendations for use of updated bivalent vaccines to children aged ≥6 months. mRNA COVID-19 vaccine effectiveness (VE) against emergency department or urgent care (ED/UC) encounters was evaluated within the VISION Network during July 4, 2022-June 17, 2023, among children with COVID-19-like illness aged 6 months-5 years. Among children aged 6 months-5 years who received molecular SARS-CoV-2 testing during August 1, 2022-June 17, 2023, VE of 2 monovalent Moderna doses against ED/UC encounters was 29% (95% CI = 12%-42%) ≥14 days after dose 2 (median = 100 days after dose 2; IQR = 63-155 days). Among children aged 6 months-4 years with a COVID-19-like illness who received molecular testing during September 19, 2022-June 17, 2023, VE of 3 monovalent Pfizer-BioNTech doses was 43% (95% CI = 17%-61%) ≥14 days after dose 3 (median = 75 days after dose 3; IQR = 40-139 days). Effectiveness of ≥1 bivalent dose, comparing children with at least a complete primary series and ≥1 bivalent dose to unvaccinated children, irrespective of vaccine manufacturer, was 80% (95% CI = 42%-96%) among children aged 6 months-5 years a median of 58 days (IQR = 32-83 days) after the dose. All children should stay up to date with recommended COVID-19 vaccines, including initiation of COVID-19 vaccination immediately when they are eligible.
Clinical impact of the genomic landscape and leukemogenic trajectories in non-intensively treated elderly acute myeloid leukemia patients
Authors: Ekaterina Jahn, Maral Saadati, Pierre Fenaux, Marco Gobbi, Gail J. Roboz, Lars Bullinger, Pavlo Lutsik, Anna Riedel, Christoph Plass, Nikolaus Jahn, Claudia Walter, Karlheinz Holzmann, Yong Hao, Sue Naim, Nicholas Schreck, Julia Krzykalla, Axel Benner, Harold N. Keer, Mohammad Azab, Konstanze Döhner, Hartmut Döhner
Journal: Leukemia (2023)

To characterize the genomic landscape and leukemogenic pathways of older, newly diagnosed, non-intensively treated patients with AML and to study the clinical implications, comprehensive genetics analyses were performed including targeted DNA sequencing of 263 genes in 604 patients treated in a prospective Phase III clinical trial. Leukemic trajectories were delineated using oncogenetic tree modeling and hierarchical clustering, and prognostic groups were derived from multivariable Cox regression models. Clonal hematopoiesis-related genes (ASXL1, TET2, SRSF2, DNMT3A) were most frequently mutated. The oncogenetic modeling algorithm produced a tree with five branches with ASXL1, DDX41, DNMT3A, TET2, and TP53 emanating from the root suggesting leukemia-initiating events which gave rise to further subbranches with distinct subclones. Unsupervised clustering mirrored the genetic groups identified by the tree model. Multivariable analysis identified FLT3 internal tandem duplications (ITD), SRSF2, and TP53 mutations as poor prognostic factors, while DDX41 mutations exerted an exceptionally favorable effect. Subsequent backwards elimination based on the Akaike information criterion delineated three genetic risk groups: DDX41 mutations (favorable-risk), DDX41
Epidemiologic and Clinical Features of Mpox in Adults Aged &gt;50 Years — United States, May 2022–May 2023
Authors: Patrick C. Eustaquio, LaTweika A.T. Salmon-Trejo, Lisa C. McGuire, Sascha R. Ellington
Journal: MMWR Morbidity and Mortality Weekly Report (2023)

During May 2022-May 2023, approximately 30,000 mpox cases were reported in the United States, predominantly among young adult men.Persons aged >50 years might experience more severe mpox disease because of a higher prevalence of comorbidities.Conversely, they could have residual protection from childhood smallpox vaccination against monkeypox virus infection and severe mpox, as has been suggested by investigation of some previous mpox outbreaks.To examine the characteristics of mpox cases among adults aged >50 years, analysts compared mpox epidemiology and clinical outcomes among all adults aged ≥18 years, by age group.Further, outcomes were compared among adults aged >50 years by JYNNEOS vaccination status.During May 10, 2022-May 17, 2023, among 29,984 adults with probable or confirmed mpox reported to CDC, 2,909 (9.7%) were aged >50 years, 96.3% of whom were cisgender men.Compared with adults aged 18-50 years, adults aged >50 years had higher prevalences of immunocompromising conditions (p<0.001) and HIV infection (p<0.001).Among adults with mpox aged >50 years, 27.6% had received JYNNEOS vaccination; this group had lower prevalences of constitutional symptoms (p<0.001),pruritus (p<0.001), and hospitalization (p = 0.002) compared with those who had not received JYNNEOS vaccine.Currently recommended JYNNEOS vaccination among all adults at risk for mpox should be encouraged, irrespective of childhood smallpox vaccination status.
Baseline innate and T cell populations are correlates of protection against symptomatic influenza virus infection independent of serology
Authors: Robert C. Mettelman, Aisha Souquette, Lee-Ann Van de Velde, Kasi Vegesana, E. Kaitlynn Allen, Christina M. Kackos, Sanja Trifkovic, Jennifer DeBeauchamp, Taylor L. Wilson, Deryn G. St. James, Smrithi S. Menon, Timothy Wood, Lauren Jelley, Richard J. Webby, Q. Sue Huang, Paul G. Thomas, Judy Bocacao, Jacqui Ralston, Jessica Danielewicz, Wendy Gunn, Nayyereh Aminisani, Ben Waite, R. Pamela Kawakami, Annette Nesdale, Michelle Balm, Nikki Turner, Tony Dowell
Journal: Nature Immunology (2023)
Ipilimumab with or without nivolumab in PD-1 or PD-L1 blockade refractory metastatic melanoma: a randomized phase 2 trial
Authors: Ari VanderWalde, Shay L. Bellasea, Kari L. Kendra, Nikhil I. Khushalani, Katie M. Campbell, Philip O. Scumpia, Lawrence F. Kuklinski, Frances Collichio, Jeffrey A. Sosman, Alexandra Ikeguchi, Adrienne I. Victor, Thach-Giao Truong, Bartosz Chmielowski, David C. Portnoy, Yuanbin Chen, Kim Margolin, Charles Bane, Constantin A. Dasanu, Douglas B. Johnson, Zeynep Eroglu, Sunandana Chandra, Egmidio Medina, Cynthia R. Gonzalez, Ignacio Baselga-Carretero, Agustin Vega-Crespo, Ivan Perez Garcilazo, Elad Sharon, Siwen Hu-Lieskovan, Sapna P. Patel, Kenneth F. Grossmann, James Moon, Michael C. Wu, Antoni Ribas
Journal: Nature Medicine (2023)
Idecabtagene vicleucel for relapsed and refractory multiple myeloma: post hoc 18-month follow-up of a phase 1 trial
Authors: Yi Lin, Noopur S. Raje, Jesús G. Berdeja, David S. Siegel, Sundar Jagannath, Deepu Madduri, Michaela Liedtke, Jacalyn Rosenblatt, Marcela V. Maus, Monica Massaro, Fabio Petrocca, Ashish Yeri, Olivia Finney, Andrea Caia, Zhihong Yang, Nathan Martin, Timothy B. Campbell, Julie Rytlewski, Jaymes Fuller, Kristen Hege, Nikhil C. Munshi, James N. Kochenderfer
Journal: Nature Medicine (2023)

Idecabtagene vicleucel (ide-cel) is a B-cell-maturation antigen (BCMA)-directed chimeric antigen receptor T cell therapy. We performed a post hoc analysis of a single-arm phase 1 multicenter study in relapsed/refractory multiple myeloma (CRB-401) (n = 62; median follow-up, 18.1 months). The primary endpoint was safety outcomes, and secondary endpoints included overall response rate (ORR), complete response (CR) and very good partial response (VGPR). The study met its primary endpoint with low rates of grade 3/grade 4 cytokine release syndrome (6.5%) and neurotoxicity (1.6%). ORR was 75.8%; 64.5% achieved VGPR or better and 38.7% achieved CR or stringent CR. Among exploratory endpoints, median duration of response, progression-free survival (PFS) and overall survival were 10.3, 8.8 and 34.2 months, respectively, and ide-cel expansion in blood and bone marrow correlated with clinical efficacy and postinfusion reduction of soluble BCMA. Patients with PFS ≥ 18 months had more naive and less exhausted T cells in apheresis material and improved functional T cell phenotype in the drug product compared with those with less durable responses. These results confirm ide-cel safety, tolerability and efficacy and describe T cell qualities that correlate with durable response. Clinicaltrials.gov identifier : NCT02658929 . This is a post hoc 18-month follow-up analysis of the CRB-401 trial, testing idecabtagene vicleucel (ide-cel, bb2121) in relapsed and refractory multiple myeloma, and reports sustained safety and clinical efficacy, which correlates with T cell phenotypes.
Genetic insights into human cortical organization and development through genome-wide analyses of 2,347 neuroimaging phenotypes
Authors: Varun Warrier, Eva-Maria Stauffer, Qin Qin Huang, Emilie M. Wigdor, Eric A. W. Slob, Jakob Seidlitz, Lisa Ronan, Sofie L. Valk, Travis T. Mallard, Andrew D. Grotzinger, Rafael Romero-Garcia, Simon Baron-Cohen, Daniel H. Geschwind, Madeline A. Lancaster, Graham K. Murray, Michael J. Gandal, Aaron Alexander-Bloch, Hyejung Won, Hilary C. Martin, Edward T. Bullmore, Richard A. I. Bethlehem
Journal: Nature Genetics (2023)
Developmental changes in exploration resemble stochastic optimization
Authors: Anna P. Giron, Simon Ciranka, Eric Schulz, Wouter van den Bos, Azzurra Ruggeri, Björn Meder, Charley M. Wu
Journal: Nature Human Behaviour (2023)

Human development is often described as a 'cooling off' process, analogous to stochastic optimization algorithms that implement a gradual reduction in randomness over time. Yet there is ambiguity in how to interpret this analogy, due to a lack of concrete empirical comparisons. Using data from n = 281 participants ages 5 to 55, we show that cooling off does not only apply to the single dimension of randomness. Rather, human development resembles an optimization process of multiple learning parameters, for example, reward generalization, uncertainty-directed exploration and random temperature. Rapid changes in parameters occur during childhood, but these changes plateau and converge to efficient values in adulthood. We show that while the developmental trajectory of human parameters is strikingly similar to several stochastic optimization algorithms, there are important differences in convergence. None of the optimization algorithms tested were able to discover reliably better regions of the strategy space than adult participants on this task.
Liraglutide restores impaired associative learning in individuals with obesity
Authors: Ruth Hanssen, Lionel Rigoux, Bojana Kuzmanovic, Sandra Iglesias, Alina C. Kretschmer, Marc Schlamann, Kerstin Albus, Sharmili Edwin Thanarajah, Tamara Sitnikow, Corina Melzer, Oliver A. Cornely, Jens C. Brüning, Marc Tittgemeyer
Journal: Nature Metabolism (2023)

Survival under selective pressure is driven by the ability of our brain to use sensory information to our advantage to control physiological needs. To that end, neural circuits receive and integrate external environmental cues and internal metabolic signals to form learned sensory associations, consequently motivating and adapting our behaviour. The dopaminergic midbrain plays a crucial role in learning adaptive behaviour and is particularly sensitive to peripheral metabolic signals, including intestinal peptides, such as glucagon-like peptide 1 (GLP-1). In a single-blinded, randomized, controlled, crossover basic human functional magnetic resonance imaging study relying on a computational model of the adaptive learning process underlying behavioural responses, we show that adaptive learning is reduced when metabolic sensing is impaired in obesity, as indexed by reduced insulin sensitivity (participants: N = 30 with normal insulin sensitivity; N = 24 with impaired insulin sensitivity). Treatment with the GLP-1 receptor agonist liraglutide normalizes impaired learning of sensory associations in men and women with obesity. Collectively, our findings reveal that GLP-1 receptor activation modulates associative learning in people with obesity via its central effects within the mesoaccumbens pathway. These findings provide evidence for how metabolic signals can act as neuromodulators to adapt our behaviour to our body's internal state and how GLP-1 receptor agonists work in clinics.
P939: THE RELATIONSHIP OF BONE MARROW FIBROSIS WITH EXTRAMEDULLARY DISEASE IN MULTIPLE MYELOMA
Authors: Hilal Konyaoglu, Ali Yilmaz Altay, Emine Göknur Işik, Beyza Oluk, Nigar Taghiyeva, Elif Sakci, Simge Erdem, Gülçin Yeğen, İpek Yönal Hindilerden, Mustafa Nuri Yenerel, Meliha Nalcaci, Sevgi Kalayoglu Besisik
Journal: HemaSphere (2023)

Topic: 14. Myeloma and other monoclonal gammopathies - Clinical Background: Bone marrow fibrosis in multiple myeloma (MM) is not uncommon at diagnosis and its presence was found to be with inferior survival. Extramedullary myeloma (EMM) developed in up to 30% of MM across the disease course and contributes a heterogeneous clinical picture in association with adverse prognostic factors (i.e., high lactate dehydrogenase level, 17p deletion and high-risk gene expression profile). Aims: We retrospectively analyzed the bone marrow fibrosis incidence of MM patients at diagnosis and evaluated the association of fibrosis with EMM. Methods: 276 MM patients whose data were evaluable at diagnosis included in the study. Bone marrow fibrosis graded according to the WHO criteria and international staging system (ISS) score data were collected electronically from hospital automated system. For EMM, positron emission tomography/computed tomography (PET-CT) imaging was used with exclusion of direct extension from skeletal tumors. Results: The gender distribution was almost similar as being 145/131 male to female. The mean age was 60.7 years (26-88). Increased fibrosis was seen in 106 of cases (38.4%) and EMD in 40 (14.5%) cases. There was a statistically significant correlation between increased bone marrow fibrosis and having EMM (<0.001). The EMM did not have a significant association with mean blood cell count, albumin, beta 2 microglobulin level, glomerular filtration rate and proteinuria. On the other hand, serum calcium and LDH levels were found to be statistically significantly higher in patients with EMM (p< 0.001). International Staging System (ISS) stages were calculated as stage I in 95 patients (34.4%), stage II in 63 patients (22.8%), and stage III in 73 patients (26.4%). There was not a statistical association with EMM and ISS. We also found that the ISS score did not correlate with bone marrow fibrosis. Summary/Conclusion: The data among extramedullary myeloma in MM is scarce. The mechanisms are also poorly understood. Decreased adhesion molecule expression and increased angiogenesis may facilitate dissemination. Bone marrow structural change with this microenvironment change - fibrosis increase - may have a predictive value in these manner and may point EMM. Our findings suggest the increase in bone marrow fibrosis may predict EMM. Keywords: Multiple myeloma, Bone Marrow Fibrosis
PB1747: OUTCOME OF CHILDHOOD ALLTREATED WITH ALL BFM IC 2009 PROTOCOL
Authors: Gizem Çilsaat, Dorukcan Alkan, Baran Alkan, Mustafa Cemaloglu, Fatma Gumruk, Selin Aytac
Journal: HemaSphere (2023)

Topic: 2. Acute lymphoblastic leukemia - Clinical Background: Acute lymphoblastic leukemia (ALL) is the most common childhood malignancy, accounting for 25% of all childhood cancers. Management of childhood ALL has greatly improved over the past decades. Our institution has been using ALL BFM IC 2009 protocol since January, 2016 and before this time we were using Modified St Jude protocols. Aims: Our aim is to identifys clinical and laboratory findings, risk groups, and outcomes of childhood ALL treated with ALL BFM IC 2009 protocol in a single tertiary center in Turkey. Methods: In this retrospective study, patients who have been diagnosed with ALL between 01 January 2016 and 31 December 2022 were included. There were 92 patients who were eligible for the study, 43 of those were female (46,7%) and 49 were male (53,3%). Median age at diagnosis was 77 months (13-212)and 49 patients (53,3%) being older than 5 years at the time of diagnose Results: There were, 85 patients (92,4%) were diagnosed with pre-B cell and seven patients (7,6%) with T cell ALL. Six patients (6,5%) and 2 patients (2,2%) were positive for t(9,22) and t(4,11), respectively. At day 8, 10 patients (10,9%) were diagnosed as poor prednisone responder. Risk stratification assesment was done on day 1, 8, 15 and 33 according to the ALL BFM IC 2009 protocol. Twenty-five patient (27,2%) were recorded as standart risk (SR), 50 patients (54,3%) as intermediate risk (IR), 17 patients (18,5%) as high risk (HR). Central nervous system involvement at diagnosis was identified in 10 (11%) patients. Relapse was observed in eight patients (8,7%); 5 of them (62,5%) being isolated bone marrow, 2 (25%) isolated testicle and 1 (12,5%) being combined relapses (bone marrow and testicle). Seven of the relapse cases (87,5%) occured within the first 60 months of the treatment. Four patients (4,3%) died during their treatment or follow up and all were either relapse or refractory cases. Five year overall survival and event free survival rates were 93±3,and 85,4±5,2 %, respectively. When compared survival rates according to initial findings(age1-5 years and ≥6 years),gender,WBC count(<20x109/l vs ≥ 20x109/l);CNS involvement (CNS(+) vs CNS(-),day15 MRD level(<0,1% vs ≥0,1%) and risk groups were not statistically different between each groups(p>0.05). Summary/Conclusion: Acute lymphoblastic leukemia is the most common malignancy in childhood. Risk assessment, risk based therapy and adequate treatment of complications play major roles in survival. Although, 32 (36,36%) out of 88 were still on treatment, 5 year EFS and OS rates was found to be comparable with the major treatment protocols. Keywords: ALL
P584: VENETOCLAX PLUS HOMOHARRINGTONINE-BASED CHEMOTHERAPY AS FIRST-LINE TREATMENT FOR ADULTS WITH ACUTE MYELOID LEUKAEMIA: A MULTICENTRE, SINGLE-ARM, PHASE 2 TRIAL
Authors: Huafeng Wang, Min Yang, Hongyan Tong, Yinjun Lou, Honghu Zhu, Yue Han, Jiejin Qian, Liping Mao, Chunmei Yang, Ying Lu, Xinping Zhou, Lihong Shou, Haitao Meng, De Zhou, Wenjuan Yu, LI LI, Jie Jin
Journal: HemaSphere (2023)

Background: Acute myeloid leukaemia (AML) patients still have unsatisfactory clinical outcomes. Venetoclax combined with chemotherapy or azacytidine or low-dose cytarabine has shown efficacy in adults with AML. Homoharringtonine is synergistically lethal with venetoclax in acute myeloid leukemia through down regulation with MCL-1. Aims: We aimed to investigate the activity and safety of venetoclax plus homoharringtonine-based induction regimens in adults with AML. Methods: We conducted a two-stage, single-arm, phase 2 trial at four public hospitals in China. We enrolled patients aged 18–60 years with previously untreated de novo AML. Patients received induction treatment with venetoclax (100 mg on day 2, 200 mg on day 3, and 300 mg on days 4–10), homoharringtonine (2 mg/m² on days 1–5), cytarabine (100 mg/m² on days 1–5), and aclarubicin (12 mg/m² on days 1–5) (VHAA regimen). The primary endpoint was the composite complete remission rate [complete remission (CR) plus complete remission with incomplete blood cell count recovery(CRi)] after one cycle of induction treatment, assessed in the as-treated population. Secondary endpoints were bone marrow measurable residual disease by flow cytometry, event-free survival, overall survival, and adverse events. This trial is ongoing and is registered with Chinese Clinical Trial Registry, ChiCTR2100053516. Results: Between Nov 25, 2021, and Mar 23, 2021, 35 patients were assessed for eligibility and 33 were enrolled. 16 (48.5%) patients were men and 17 (51.5%) were women, and all were Asian. The composite complete remission rate after one cycle of DAV regimen was 93.9% (31 of 33 patients, with CR rate of 87.8%, 28/31) in the entire cohort. 31 (100%) of 31 patients had undetectable measurable residual disease (ie, <0.01%). Grade 3 or worse adverse events included neutropenia in 33 (100%) of 33 patients, thrombocytopenia in 33 (100%), anaemia in 33 (100%), febrile neutropenia in 11 (33.3%), pneumonia in eighteen (54.5%), and sepsis in four (12%). No treatment-related deaths occurred. Summary/Conclusion: The VHAA regimen represents an effective induction therapy for newly diagnosed adults with acute myeloid leukaemia, which resulted in a high rate of composite complete remission. These findings showing a safe strategy to incorporate venetoclax combined homoharringtonine-based induction regimens to treat newly diagnosed acute myeloid leukaemia. Keywords: Acute myeloid leukemia, Venetoclax, Chemotherapy, Homoharringtonine
Simplifying pharmacotherapy for patients with COPD: a viewpoint
Authors: Bartolome Celli, Jørgen Vestbo
Journal: European Respiratory Journal (2023)

<h3>Tweetable abstract</h3> <b>Review of simple clinical and physiological data can help stratify COPD severity and guide the pharmacotherapy most likely to improve patient outcomes. Supervision of response, adherence and correct use of medications helps adjust therapy.</b> https://bit.ly/3P3J5gf
Palliative care in COPD and ILD: a call for action
Authors: Marlies Wijsenbeek, Claudia Valenzuela, Anne Holland
Journal: European Respiratory Journal (2023)

<h3>Tweetable abstract</h3> <b>In the transforming care landscape where people get older and live longer with chronic respiratory diseases, the pulmonary community must make palliative care one of its priorities</b>https://bit.ly/3rDBbAg
Single-cell phylogenies reveal changes in the evolutionary rate within cancer and healthy tissues
Authors: Nico Borgsmüller, Monica Valecha, Jack Kuipers, Niko Beerenwinkel, David Posada
Journal: Cell Genomics (2023)

Cell lineages accumulate somatic mutations during organismal development, potentially leading to pathological states. The rate of somatic evolution within a cell population can vary due to multiple factors, including selection, a change in the mutation rate, or differences in the microenvironment. Here, we developed a statistical test called the Poisson Tree (PT) test to detect varying evolutionary rates among cell lineages, leveraging the phylogenetic signal of single-cell DNA sequencing (scDNA-seq) data. We applied the PT test to 24 healthy and cancer samples, rejecting a constant evolutionary rate in 11 out of 15 cancer and five out of nine healthy scDNA-seq datasets. In six cancer datasets, we identified subclonal mutations in known driver genes that could explain the rate accelerations of particular cancer lineages. Our findings demonstrate the efficacy of scDNA-seq for studying somatic evolution and suggest that cell lineages often evolve at different rates within cancer and healthy tissues.
CD44+ lung cancer stem cell-derived pericyte-like cells cause brain metastases through GPR124-enhanced trans-endothelial migration
Authors: Qian Huang, Liping Liu, Dakai Xiao, Zhi Huang, Wenjun Wang, Kui Zhai, Xiaoguang Fang, Jongmyung Kim, James Liu, Wenhua Liang, Jianxing He, Shideng Bao
Journal: Cancer Cell (2023)